All of the mutations occurred in a KCTD1 region encoding a highly conserved bric-a-brac, tram track, and broad complex (BTB) domain that is required for transcriptional repressor activity.

The identification of KCTD1 mutations in SEN syndrome reveals a role for this BTB-domain-containing transcriptional repressor during ectodermal development.

[12] Hu et al. have identified a mechanism whereby disease related KCTD1 mutants and AP 2α mutants may work, by disrupting their interaction with the wildtype proteins AP 2α and KCTD1 and by influencing the regulation of the Wnt/β catenin pathway.

[13] It is likely that this syndrome is inherited in an autosomal dominant fashion,[5][14] however, there may be a recessive form with hypotonia and developmental delay.

[3] There are subsequent reports of patients from the US,[4][14][18][19][20] France,[7][8][9] Australia,[5] UAE,[15] India[21] and Cuba.